This is a proposal for Phase III support of the NCRR COBRE Center for Protein Structure and Function at the University of Arkansas, which was established in October, 2000 with Phase I NIH COBRE Grant 1 P20 RR15569- 01 and continued in September, 2005 with Phase II COBRE Grant 2 P20 RR015569-06. Protein structure and function is a central biomedical research area that has great potential for leading to improvements in human health. The Center supports thematically-linked multidisciplinary research projects involving junior faculty, mid-career faculty, and senior faculty with expertise in a broad range of techniques needed to study protein structure and function. The goals of the COBRE Center are to strengthen collaboration between investigators and allow them to develop promising new approaches to biomedical research in protein structure and function. The Center has made excellent progress since its establishment in October, 2000. Thirteen outstanding new faculty members have been hired, and core facilities in NMR spectroscopy, X-ray crystallography, mass spectrometry, large-scale protein production, and chemical synthesis have been established. The five research core facilities in the Center are highly interactive, allowing an investigator to develop a project through all stages from identifying specific proteins of biomedical significance, determining the structures of these proteins and how they interact with other proteins and metabolites, and in some cases designing drugs to treat diseases associated with altered function of the proteins. The strategic plan for Phase III of our COBRE Center during the next five years is (1) to maintain and strengthen the state-of-the-art COBRE research core facilities developed during phases I and II that are essential for the support of the research projects in the Center, and (2) to support research pilot projects and training components to sustain a collaborative, multidisciplinary research environment in protein structure and function. All of the research projects supported by our COBRE Center are directed toward obtaining a detailed molecular-level understanding of the structure and function of proteins that could lead to improved treatments for human disease. For example, the goal of one project is to develop and test a fused parathyroid hormone - collagen bindng domain protein for the treatment of osteoporosis.